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Yorodumi- EMDB-23685: human ATP13A2 in the outward-facing E2 state bound to spermine an... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23685 | |||||||||
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Title | human ATP13A2 in the outward-facing E2 state bound to spermine and magnesium fluoride | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information polyamine transmembrane transporter activity / polyamine transmembrane transport / spermine transmembrane transport / peptidyl-aspartic acid autophosphorylation / regulation of ubiquitin-specific protease activity / ABC-type polyamine transporter activity / regulation of autophagosome size / extracellular exosome biogenesis / P-type ion transporter activity / regulation of chaperone-mediated autophagy ...polyamine transmembrane transporter activity / polyamine transmembrane transport / spermine transmembrane transport / peptidyl-aspartic acid autophosphorylation / regulation of ubiquitin-specific protease activity / ABC-type polyamine transporter activity / regulation of autophagosome size / extracellular exosome biogenesis / P-type ion transporter activity / regulation of chaperone-mediated autophagy / negative regulation of lysosomal protein catabolic process / regulation of autophagy of mitochondrion / regulation of lysosomal protein catabolic process / autophagosome-lysosome fusion / intracellular monoatomic cation homeostasis / autophagosome organization / protein localization to lysosome / phosphatidic acid binding / positive regulation of exosomal secretion / multivesicular body membrane / ATPase-coupled monoatomic cation transmembrane transporter activity / intracellular zinc ion homeostasis / Translocases; Catalysing the translocation of other compounds; Linked to the hydrolysis of a nucleoside triphosphate / regulation of protein localization to nucleus / cupric ion binding / lysosomal transport / regulation of endopeptidase activity / regulation of mitochondrion organization / phosphatidylinositol-3,5-bisphosphate binding / cellular response to zinc ion / regulation of intracellular protein transport / lipid homeostasis / Ion transport by P-type ATPases / autophagosome membrane / cellular response to manganese ion / regulation of macroautophagy / regulation of neuron apoptotic process / transport vesicle / autophagosome / multivesicular body / lysosomal lumen / positive regulation of protein secretion / transmembrane transport / autophagy / intracellular calcium ion homeostasis / late endosome / monoatomic ion transmembrane transport / late endosome membrane / manganese ion binding / cellular response to oxidative stress / intracellular iron ion homeostasis / vesicle / protein autophosphorylation / lysosome / neuron projection / lysosomal membrane / neuronal cell body / positive regulation of gene expression / ATP hydrolysis activity / zinc ion binding / ATP binding / membrane Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
Authors | Lee KPK | |||||||||
Funding support | 1 items
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Citation | Journal: Mol Cell / Year: 2021 Title: Structural mechanisms for gating and ion selectivity of the human polyamine transporter ATP13A2. Authors: Jordan Tillinghast / Sydney Drury / Darren Bowser / Alana Benn / Kenneth Pak Kin Lee / Abstract: Mutations in ATP13A2, also known as PARK9, cause a rare monogenic form of juvenile-onset Parkinson's disease named Kufor-Rakeb syndrome and other neurodegenerative diseases. ATP13A2 encodes a ...Mutations in ATP13A2, also known as PARK9, cause a rare monogenic form of juvenile-onset Parkinson's disease named Kufor-Rakeb syndrome and other neurodegenerative diseases. ATP13A2 encodes a neuroprotective P5B P-type ATPase highly enriched in the brain that mediates selective import of spermine ions from lysosomes into the cytosol via an unknown mechanism. Here we present three structures of human ATP13A2 bound to an ATP analog or to spermine in the presence of phosphomimetics determined by cryoelectron microscopy. ATP13A2 autophosphorylation opens a lysosome luminal gate to reveal a narrow lumen access channel that holds a spermine ion in its entrance. ATP13A2's architecture suggests physical principles underlying selective polyamine transport and anticipates a "pump-channel" intermediate that could function as a counter-cation conduit to facilitate lysosome acidification. Our findings establish a firm foundation to understand ATP13A2 mutations associated with disease and bring us closer to realizing ATP13A2's potential in neuroprotective therapy. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_23685.map.gz | 108.1 MB | EMDB map data format | |
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Header (meta data) | emd-23685-v30.xml emd-23685.xml | 14.5 KB 14.5 KB | Display Display | EMDB header |
Images | emd_23685.png | 55 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23685 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23685 | HTTPS FTP |
-Validation report
Summary document | emd_23685_validation.pdf.gz | 411.2 KB | Display | EMDB validaton report |
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Full document | emd_23685_full_validation.pdf.gz | 410.8 KB | Display | |
Data in XML | emd_23685_validation.xml.gz | 7.2 KB | Display | |
Data in CIF | emd_23685_validation.cif.gz | 8.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23685 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23685 | HTTPS FTP |
-Related structure data
Related structure data | 7m5yMC 7m5vC 7m5xC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_23685.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
+Entire : Transport protein in inhibited state 2 monomer
+Supramolecule #1: Transport protein in inhibited state 2 monomer
+Macromolecule #1: Polyamine-transporting ATPase 13A2
+Macromolecule #2: MAGNESIUM ION
+Macromolecule #3: TETRAFLUOROMAGNESATE(2-)
+Macromolecule #4: CHOLESTEROL HEMISUCCINATE
+Macromolecule #5: DODECYL-BETA-D-MALTOSIDE
+Macromolecule #6: CHOLESTEROL
+Macromolecule #7: DECANE
+Macromolecule #8: TETRADECANE
+Macromolecule #9: DODECANE
+Macromolecule #10: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #11: SPERMINE (FULLY PROTONATED FORM)
+Macromolecule #12: (2R)-3-{[(S)-hydroxy{[(1S,2R,3R,4S,5S,6R)-2,4,6-trihydroxy-3,5-bi...
+Macromolecule #13: water
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 65.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.0 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 285797 |
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Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |